11-796 Ranitidine Hydrochloride 2022

E. (2S,3aS,6aS)-I-[(2S)-2-[[(IS)-I-<:arboxy-3-
phenylpropyl]amino]propanoyl]octahydrocyclopenra[b]
L. ethyl (2S)-2-[(3S,5aS,8aS,9aS)-9a-hydroxy-3-methyl-I,4-
pyrrole-2-carboxylic acid (ramiprilar),
dioxodecahydro-2H-cyclopema[4,5]pyrrolo[I,2-a]pyrazin-
2-yl]-4-phenylbutanoate (ramipril
hydroxydikeroplperazlne),

F. (2S)-2-[[(2S)-I-ethoxy-l-oxo-4-phenylbutan-2-yl]
amino]propanoic acid,
M.(2R,3R)-2,3-bis(benzoyloxy)buranedioic acid (dibenzoyl
/""'YCH,
tartric acid),
V
G. methylbenzene (toluene),

N. (2R,3aR,6aR)-I-[(2S)-2-[[(2S)-I-ethoxy-l-oxo-4-
phenylbutan-2-yl]arnino]propanoyl]oetahydrocyclopema
[b]pyrrole-2-carboxylic acid «S,S,R,R,R)-isomer of
H. (2S,3aS,6aS)-I-[(2S)-2-[[(2R)-I-ethoxy-l-oxo-4- ramipril),
phenylbutan-2-yl]arnino]propanoyl]ocrahydrocyclopenta
[b]pyrrole-2-carboxylic acid «R,S,S,S,S)-.opimer of
ramipril),

O. diethyl (2E,2'3)-2,2'-[(2E,53)-2,5-dimethyl-3,6-
dioxopiperazine-I ,4-<1 iyl]bis( 4-phenyIbutanoare).
I. (2S,3aS,6aS)-I-[(2R)-2-[[(2S)-I-ethoxy-l-oxo-4- _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ PhE<I
phenylbutan-2-yl)amino]propanoyl]ocrahydrocyclopenra
[b]pyrrole-2-carboxylic acid «S,R,S,S,S)-epimer of
ramipril),
Ranitidine Hydrochloride ***
*** ***
(ph. Eur. monograph 0946) ***

HCI
J. (2R,3aR,6aR)-I-[(2R)-2-[[(2R)-I-ethoxy-l-ox<>-4-
phenylburan-2-yl]amino]propanoyl]octahydrocyclopenta
[b]pyrrole-2-carboxylic acid (enantiomer of ramipril),
350.9 66357-59-3

Action and use

HistamineH 2 receptor antagonist; treatment of peptic ulcer
disease.
Preparations
Ranitidine Injection
K. (2S)-2-[(3S,5aS,8aS,9aS)-3-methyl-I,4-<1ioxodecahydro- Ranitidine Oral Solution
2H-cyclopenta[4,5] pyrrolo [1, 2-a]pyrazin-2-yl]-4- Rartitidine Tablets
phenylbutanoic acid (ramiprilate diketopiperazine), Ranitidine Effervescent Tablets

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 2022 Ranitidine Hydrochloride II-797

PhE"
DEFINITION
N-[2-[[[5-[(Dimethylamino)methyl]furan-2-yl]
methyl] sulfanyl]ethyl]-N'-methyl-2-nitroeth-I-ene-1, 1-
diamine hydrochloride.
Content
98.5 per cent to 101.5 per cent (dried substance).
CHARACTERS
Appearance
White or pale yellow, crystalline powder, hygroscopic.
Solubility
Freely soluble in water, sparingly soluble or slightly soluble in
anhydrous ethanol, very slightly soluble in methylene
chloride.
It shows polymorphism (5.9).
IDENTIFICATION
A.lnfrared absorption spectrophotometry (2.2.24).
Comparison ranitidine hydrochloride CRS.
If the spectra obtained in the solid state show differences,
dissolve 10 mg of the substance to be examined and 10 mg
of the reference substance separately in 0.5 mL of methanolR
in an agate mortar. Evaporate to dryness under a stream of
niirogen R. Dry the residues under vacuum for 30 min.
Add 3 drops of liquidparaffinR to the residues and triturate
until the mull shows a milky appearance. Compress the mulls
between 2 plates transparent to infrared radiation and record
new spectra.
B. It gives reaction (a) of chlorides (2.3.1).
TESTS
Solution S
Dissolve 1.0 g in carbon dioxide-free water R and dilute to
100.0 mL with the same solvent.
Appearance of solution
Solution S is clear (2.2.1) and not more intensely coloured
than reference solution BY, (2.2.2, Method 1/).
pH (2.2.3)
4.5 to 6.0 for solution S.
Related substances
Liquid chromatography (2.2.29).
Buffer solutiOn Dissolve 6.8 g of potassium dihydrogen
phosphate R in 950 mL of warer for chromatography R. Adjust
to pH 7.1 with strong sodium hydroxide solution R and dilute to
1000 mL with waterfor chromatography R.
Test solution Dissolve 13 mg of the substance to be
examined in mobile phase A and dilute to 100.0 mL with
mobile phase A.
Reference solution (a) Dissolve 6.5 mg of ranitidine for
impurityA identification CRS in mobile phase A and dilute to
50 mL with mobile phase A.
Reference solution (b) Dilute 1.0 mL of the test solution to
100.0 mL with mobile phase A. Dilute 1.0 mL of this
solution to 10.0 mL with mobile phase A.
Reference solution (c) Dissolve the contents of a vial of
ranitidine impun'ty J CRS in 1 mL of the test solution.
Blank solution Mobile phase A.
Column:
- size: 1= 0.10 m, 0 =: 4.6 mrn;
- stationary phase: end-capped oaadecytsily/ amorphous
arganosi/ica polymer for chromawgraphy R (3.5 urn);
temperature: 35 "C.
_
Mobile phase:
- mobile phase A: acetonitrile for chromawgraphy R, buffer
solution (2:98 VII');
- mobile phase B: acetonitrile for chromatography R, buffer
solution (22:78 VII');
Time Mobile phase A MobUe phase B
(mIn) (per cent I'IJI) (per cent VIJI)
0·10 100 ---> 0 0---> 100
10 - 15 o 100
Flow rate 1.5 mUmin.
Detection Spectrophotometer at 230 run.
Injection I 0
Identification of impurities Use the chromatogram supplied
with ranitidine for impw;ty A identification CRS and the
chromatogram obtained with reference solution (a) to
identify the peak due to impurity A; use the chromatogram
obtained with reference solution (c) to identify the peak due
to impurity J.
Relative retention With reference to ranitidine (retention
=
time about 7 min): impurity J about 0.9; =
impurity A = about I. 7.
System suitaln1ity:
- resolution: minimum 1.5 between the peaks due to
impurity J and ranitidine in the chromatogram obtained
with reference solution (c)j
- me chromatogram obtained with the blank solution does
not show any peak with the same relative retention as the
peak due to impurity A in the chromatogram obtained
with reference solution (a).
Cakulation 0/percentage contents:
- correction factor: multiply the peak area of impurity J by
2.0;
- for each impurity, use the concentration of ranitidine
hydrochloride in reference solution (b).
Limits:
- impun'ty A: maximum 0.3 per cent;
- impurityJ: maximum 0.15 per cent;
- unspecified impurities: for each impurity, maximum
0.10 per cent;
- total: maximum 0.5 per 'cent;
- reponing threshold: 0.05 per cent.
Loss on drying (2.2.32)
Maximum 0.75 per cent, determined on 1.000 g by drying in
vacuo at 60 °C at a pressure not exceeding 0.1 kPa.
Sulfated ash (2.4.14)
Maximum 0.1 per cent, determined on 1.0 g.
ASSAY
Dissolve 0.280 g in 35 mL of warer R. Titrate with 0.1 M
sodium hydroxide, determining the end-point
potentiometrically (2.2.20).
1 mL of 0.1 M sodium hydroxide is equivalent to 35.09 mg of
C"H"CIN.03 S.
STORAGE
In airtight container, protected from light.
L'dPURITIES
Specified impurities A, J.
Otherdetectable impurities (thefollowing subsumces 'WOuld, if
present at a sufficient level, be detected by qne or otherof the tests
in the monograph. They are limited by the general acceptance
criterion for otherhmspecified impurities and/or by the general

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 II-798 Rapeseed Oil 2022

monograph Substances for pharmaceutical use (2034). It is

therefore tlot necessary to identify these impurices for
demonstration of compliance. See also 5.10. Conll'Ol of impurities
in substances for pharmaceutical use) B, C, D, E, F, G, H,
I, K. H. N-methyl-2-nitroacetamide,

A. N,N' -bis[2- [[[5-[(d imethylamino) methyl] furan-2-yl]

methyl]sulfanyl] ethyl]-2-nitroeth-l-ene-l, f-diamine,
I. 2,2'-methylenebis[N-[2-[[[5-[(dimethylamino)
methyl] furan-2-yl]methyl] sulfanyl]ethyl]-N'-methyl-2-
nitroeth-l-ene-I, J-diamine],

B. 2- [[[5- [(dime thylamino)methyl] furan-2-yl]methyl] sulfa nyl]

ethan-Lamine,
J. N,N" -[methYlenebis(sulfanediylethan-2,I-diyl)]bis(N'-
methy I-2-nitroe rh-f-ene-I, l-diamine),

c. N-[2-[[[5-[(dimethylamino)methyl]furan-2-yl]methyl]
sulfinyl] ethyl]-N'-methyl- 2-nirroeth-I-ene-I, f-dlamine,
K. N-methyl-I-(methylsulfanyl)-2-nirroeth-l-en-l-amine.
__________________

Refined Rapeseed Oil

D. N-[2-[[[5-[(dimethylamino)methyl]furan-2-yl]methYI] (Ph. Bur. monograph 1369)
sulfanyljethylj-z-nitroacetamlde, PhE" _

DEFINITION
Fatty oil obtainedfrom the seeds of Brassica napus L.
and Brassica campeseis L. by mechanical expression or by
extraction. It is then refined. A suitable antioxidant may be
added.
CHARACTERS
Appearance
E. [5-[[[2-[[ I-(methylamino)-2-nitroeth-l-en-l-yl]amino]
Clear, light yellow liquid.
ethyl]sulfanyl]methyl]furan-2-yl]-N,N-
dimethylmethanamine N-oxide, Solubility
Practically insoluble in water and in ethanol (96 per cent),
miscible with light petroleum (bp: 40-60 "C).
Relative density
About 0.917.
Refractive index
About 1.473.
F. [5-[(dimethylamino)methyl]furan-2-yl]methanol, IDENTIFICATION
Identification of fatty oils by thin-layer chromatography
(2.3.2).
Results The chromatogram obtained is similar to the
corresponding chromatogram shown in Figure 2.3.2.-l.
TESTS
G. [3-(methylamino)-5,6-dihydro-2H-I,4-thiazin-2-ylidene] Acid value (2.5.1)
hydroxylamine, Maximum 0.5, determined on 10.0 g.

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